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In 1964, Naked Snake, after knocking out Major Raikov and stealing his uniform, placed him inside of a locker to hide him from the enemy as he uses his uniform to infiltrate the Groznyj Grad weapons lab's west wing to rescue Nikolai Stepanovich Sokolov. After returning to this locker, he also retrieved the black Sneaking Suit prototype. He also procured a maintenance crew disguise in another locker within the same room.

In 1970, Elisa advised Naked Snake to hide in a locker in the preparation chamber of San Hieronymo Peninsula's research laboratory during the San Hieronymo Takeover, when various soldiers were sweeping the area after it became apparent that an intruder was in the area.

In 1999, Gustava Heffner placed a tape of Zanzibar Land's national anthem inside a locker prior to her death. Solid Snake then accessed it and found it inside. Some of the children in Zanzibar Land played inside other nearby lockers in a games of "hide and seek." Dr. Kio Marv, before his death, placed a Konami MSX cartridge, which actually housed a microfilm containing the OILIX formula, inside a locker within his confinement facility, which Snake later located and retrieved.

When the Cyborg Ninja (Gray Fox) confronted a terrified Hal Emmerich, in his lab on Shadow Moses Island, the latter hid inside a locker. The Ninja commented that Emmerich could watch his and Snake's battle from inside. After Snake drove the Ninja away, he convinced Emmerich to leave his hiding place.

The player can hit open lockers by hitting them enough times. Doing this will often causes the door to fall towards them, knocking them down. There are some locked lockers that can only be opened by using this method. However, some doors will fall inwards, denying access to that locker.

In Metal Gear Solid 2, during the Plant chapter, the player will encounter two unconscious Gurlukovich soldiers. They'll normally wake up upon logging into the node for the first time, though it's possible to bypass this by stuffing their bodies in the lockers beforehand. Putting enemies in a locker in the HD version will unlock the achievement trophy "Hurt Locker", referring to the 2003 Iraq War film of the same name.